Genetic Mutations in Cancer Susceptibility Genes: A Family History of Cancer

Abstract Background Hereditary cancer susceptibility syndrome (HCSS) contributes to the cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and refer the patients and their families for genetic counselling. The study aimed to identify ALL patients who meet the American College of Medical Genetics (ACMG) criteria and refer them for the genetic testing for HCSS as hereditary leukemia and hematologic malignancy syndrome, and to elucidate the significance of high consanguinity with the prevalence of inherited leukemia in Pakistani population. Methods A total of 300 acute lymphoblastic leukemia patients were recruited from the Children’s Hospital, Lahore, Pakistan from December 2018 to September 2019. A structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection. Results In our cohort, 60.40% of ALL patients were identified to meet ACMG criteria. Among them, a large number of patients (40.65%) solely fulfil the criteria due to the presence of parental consanguinity. However, parental consanguinity showed protective impact on the onset at early age of disease [OD = 0.44 (0.25–0.77), p-value = 0.00] while, a family history of cancer increased the risk of cardiotoxicity [OD = 2.46 (1.15–5.24), p-value = 0.02]. Parental consanguinity shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions More than 50% of the ALL patients were considered the strong candidates’ for genetic testing of HCSS in the Pakistani population, and parental consanguinity was the leading criteria fulfilled by the individuals when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines, especially for the criterion of parental consanguinity, and formulating the score based criteria based on; genetic research, the toxicology profile, physical features, personal and family history of cancer for the identification of patients for the genetic testing.

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Algorithm of monitoring of patients with family history of cancer as a method of cancer prevention

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1542 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1542-1542

Author(s):

V. D. Petrova ◽

T. V. Sinkina ◽

N. A. Zarubina ◽

S. A. Terekhova ◽

J. N. Dimitriadi ◽

...

Keyword(s):

Family History ◽

Cancer Prevention ◽

Hereditary Cancer ◽

Cancer Susceptibility ◽

Molecular Genetic ◽

Health Examination ◽

Genetic Tests ◽

Family History Of Cancer ◽

History Of ◽

History Of Cancer

1542 Background: Existent genetic tests are not able to provide effective forecasting of all cancer sites and all those methods are generally expensive. At the same time approximately 50% of population has cancer susceptibility and 10% - hereditary cancer syndromes. The purpose of this study was to develop the algorithm of monitoring to provide effective forecasting and prevention of cancer in patients with hereditary cancer susceptibility. Methods: The algorithm of monitoring of patients with family history of cancer includes 2 stage: I - diagnostic, II - treatment and rehabilitation. In the I stage patients with 3 and more relatives by blood who had cancers of any site are revealed by oncologist. Their genealogical trees are analyzed by geneticist. All those patients are registered in the registry of “cancer”-families’ members, interviewed and got all the necessary diagnostic procedures with the following multivariative analysis (of more than 200 geno- and phenotypic characteristics). Patients with determined high risk of malignancies undergo deep clinical and instrumental examination, site-by-site searching for cancer, molecular genetic tests. In the II stage individual recommendations for the patients are developed, pretumour lesions are treated, preventative surgery is performed (resection of a target organ) and the measures for strengthening of anti-tumour resistance are taken. All the patients of the registry get the periodic health examination for term of life: preventive examination once per 6 months, multivariative analysis once per 3 years. Results: The registry of “cancer”-families’ members included 421 families - 1833 patients (232 men and 1601 women at the age of 28–74). In 2003–2006 there were revealed obligatory pre-cancer lesions in 637 patients, cancers in situ - in 45 patients, and cancers of different sites - in 69 patients (in I stage - 78.3%, II stage - 18.9%, III stage - 2.8%, IV stage - 0). Conclusions: This algorithm of monitoring of the patients from the registry of “cancer”-families’ members made it possible to provide high effectiveness of cancer prevention and early detection. No significant financial relationships to disclose.

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Stability of Self-Reported Family History of Prostate Cancer Among African American Men

Journal of Nursing Measurement ◽

10.1891/jnum.10.1.39.52547 ◽

2002 ◽

Vol 10 (1) ◽

pp. 39-46 ◽

Cited By ~ 11

Author(s):

Sally P. Weinrich ◽

Louise Faison-Smith ◽

Julie Hudson-Priest ◽

Charmaine Royal ◽

Isaac Powell

Keyword(s):

Prostate Cancer ◽

African American ◽

Family History ◽

Low Income ◽

Susceptibility Testing ◽

Cancer Susceptibility ◽

African American Men ◽

Family History Of Cancer ◽

History Of ◽

History Of Cancer

The genome-wide search for the prostate cancer gene holds the promise of the availability of prostate cancer susceptibility testing in the near future. When this occurs, self-reported history of prostate cancer will be critical in determining who is eligible for cancer susceptibility testing. Little attention has been given to the reliability of self-reported family history of prostate cancer, particularly in African American men. This correlational study measured the stability of self-reported family history of prostate cancer over a one-year time period (between 1997 and 1998) with 96 African American men from a southern state. The men were asked on two separate occasions, 1 year apart, “Have any of your men blood relatives ever had prostate cancer?” The question had a prior test-retest reliability of 0.85 over a 2-week period. Forty-eight percent of the men changed their answers on the second administration. Men most likely to change their answers were low-income men and men who did not participate in a free prostate cancer screening. This research highlights the need for public genetic education and the recognition by health professionals that self-reported family history of cancer is a variable that changes as families have increased awareness and communication concerning family history of cancer.

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Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.3502 ◽

2017 ◽

Vol 35 (30) ◽

pp. 3382-3390 ◽

Cited By ~ 121

Author(s):

Koji Shindo ◽

Jun Yu ◽

Masaya Suenaga ◽

Shahriar Fesharakizadeh ◽

Christy Cho ◽

...

Keyword(s):

Pancreatic Cancer ◽

Family History ◽

Germline Mutation ◽

Cancer Susceptibility ◽

Germline Mutations ◽

Susceptibility Genes ◽

Familial Pancreatic Cancer ◽

Cancer Susceptibility Genes ◽

Periampullary Neoplasms ◽

History Of

Purpose Deleterious germline mutations contribute to pancreatic cancer susceptibility and are well documented in families in which multiple members have had pancreatic cancer. Methods To define the prevalence of these germline mutations in patients with apparently sporadic pancreatic cancer, we sequenced 32 genes, including known pancreatic cancer susceptibility genes, in DNA prepared from normal tissue obtained from 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection at Johns Hopkins Hospital between 2000 and 2015. Results Thirty-three (3.9%; 95% CI, 3.0% to 5.8%) of 854 patients with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known familial pancreatic cancer susceptibility genes: BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients), PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient). Patients with these germline mutations were younger than those without (mean ± SD, 60.8 ± 10.6 v 65.1 ± 10.5 years; P = .03). Deleterious germline mutations were also found in BUB1B (1) and BUB3 (1). Only three of these 33 patients had reported a family history of pancreatic cancer, and most did not have a cancer family history to suggest an inherited cancer syndrome. Five (1.7%) of 288 patients with other periampullary neoplasms also had a deleterious germline mutation. Conclusion Germline mutations in pancreatic cancer susceptibility genes are commonly identified in patients with pancreatic cancer without a significant family history of cancer. These deleterious pancreatic cancer susceptibility gene mutations, some of which are therapeutically targetable, will be missed if current family history guidelines are the main criteria used to determine the appropriateness of gene testing.

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Racial/Ethnic Differences in the Association Between Family History of Cancer and Smoking Status Among US Adults

Annals of Epidemiology ◽

10.1016/j.annepidem.2020.08.025 ◽

2020 ◽

Vol 52 ◽

pp. 103-104

Author(s):

I. Jackson ◽

K. Okhawere ◽

G. Oboli ◽

A. Opiegbe ◽

O. Eromosele

Keyword(s):

Family History ◽

Ethnic Differences ◽

Smoking Status ◽

Family History Of Cancer ◽

History Of ◽

Racial Ethnic ◽

History Of Cancer

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Family history of cancer in first degree relatives and risk of cancer of unknown primary

European Journal of Cancer Care ◽

10.1111/ecc.13485 ◽

2021 ◽

Author(s):

Alexander L. R. Grewcock ◽

Karlijn E. P. E. Hermans ◽

Matty P. Weijenberg ◽

Piet A. Brandt ◽

Caroline Loef ◽

...

Keyword(s):

Family History ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Family History Of Cancer ◽

First Degree Relatives ◽

History Of ◽

Risk Of Cancer ◽

History Of Cancer

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Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer

Cells ◽

10.3390/cells10030631 ◽

2021 ◽

Vol 10 (3) ◽

pp. 631

Author(s):

Karin Alvarez ◽

Alessandra Cassana ◽

Marjorie De La Fuente ◽

Tamara Canales ◽

Mario Abedrapo ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Age Of Onset ◽

Late Onset ◽

Molecular Characteristics ◽

Family History Of Cancer ◽

Molecular Features ◽

Age Of Diagnosis ◽

History Of ◽

History Of Cancer

Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.

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